This study will evaluate the role of bronchial responsiveness (BR), host immunological status and familial concordance in the etiology and natural history of airway obstructive diseases (AOD) in a multistage stratified cluster sample (using county employees as index cases for families). The effects of acute exposures on BR and immunological markers will be assessed, as well as their roles in inducing longitudinal changes in lung function and symptoms, diagnoses. The risk of bronchial responsiveness in initial and late stages of AOD will be assessed. Asthma and wheeze symptoms at different stages of life will be related to bronchial responsiveness, lung function status, and the development of AOD. We will specifically examine the presence of occult bronchial responsiveness in AOD that occur at different ages and the combined factors that lead to chronic symptoms and decrements in lung function. The effects of mediation on bronchial responsiveness, symptoms and changes in lung function will be assessed. The study will evaluate the interactions of bronchial responsiveness, host immunological status, smoking, environmental and occupational exposures in these processes. Population genetic characteristics will be evaluated. It will study further the development, course and antecedent conditions and patterns of what appear to be (from our prior studies) the two major types of AOD. The relatively stereotyped form ("COPD") with a rapid fall in pulmonary function, usually in heavy smokers with no apparent antecedent immunological factors; and the more variable form ("chronic asthmatic bronchitis") in those with "asthmatic" predisposing immunological characteristics. The predictive value of the FEV1/FVC ratio will be included in these further studies. The study will evaluate the different risk factors and their effects in young adults, prior to frank clinical AOD, and in middle age, in which the rapid declines and onset of clinical AOD usually are manifest. The role of different immunological factors in producing or mediating the effects of smoking, such as the high IgE in smokers, will be explored further; it is thought that dysfunction related to smoking is associated with a high IgE, which is related to a rapid decline in pulmonary function even in the presence of asthmatic or bronchitic symptoms. Other immunoglobulins will be evaluated in this regard (e.g. secretory A, IgG) as they interact with IgE in these processes, especially in regard to chronic changes.